Selenium-binding protein 1: Its physiological function, dependence on aryl hydrocarbon receptors, and role in wasting syndrome by 2,3,7,8-tetrachlorodibenzo-p-dioxin

• Published in: Biochimica et biophysica acta 2013-06, Vol.1830 (6), p.3616-3624
• Main Authors: Tsujimoto, Sayuri, Ishida, Takumi, Takeda, Tomoki, Ishii, Yuji, Onomura, Yuko, Tsukimori, Kiyomi, Takechi, Shinji, Yamaguchi, Tadatoshi, Uchi, Hiroshi, Suzuki, Satoshi O., Yamamoto, Midori, Himeno, Masaru, Furue, Masutaka, Yamada, Hideyuki
• Format: Article
• Language: English
• Subjects: 2,3,7,8-Tetrachlorodibenzo-p-dioxin; animal models; animal ovaries; Animals; Aryl hydrocarbon receptor; carcinoma; CDC2 Protein Kinase - genetics; CDC2 Protein Kinase - metabolism; DNA microarrays; Female; genes; Knockout mouse; Male; Mice; Mice, Knockout; Ovarian cancer; Ovarian Neoplasms - chemically induced; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovary - metabolism; Ovary - pathology; phenotype; Polychlorinated Dibenzodioxins - adverse effects; Polychlorinated Dibenzodioxins - pharmacology; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; receptors; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; Selenium-binding protein 1; Selenium-Binding Proteins - genetics; Selenium-Binding Proteins - metabolism; Teratogens - pharmacology; tetrachlorodibenzo-p-dioxin; toxicity; Wasting syndrome; Wasting Syndrome - chemically induced; Wasting Syndrome - genetics; Wasting Syndrome - metabolism
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.03.008

Selenium-binding protein 1 (Selenbp1) is suggested to play a role in tumor suppression, and may be involved in the toxicity produced by dioxin, an activator of aryl hydrocarbon receptors (AhR). However, the mechanism or likelihood is largely unknown because of the limited information available about the physiological role of Selenbp1. To address this issue, we generated Selenbp1-null [Selenbp1 (−/−)] mice, and examined the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in this mouse model. Selenbp1 (−/−) mice exhibited only a few differences from wild-type mice in their apparent phenotypes. However, a DNA microarray experiment showed that many genes including Notch1 and Cdk1, which are known to be enhanced in ovarian carcinoma, are also increased in the ovaries of Selenbp1 (−/−) mice. Based on the different responses to TCDD between C57BL/6J and DBA/2J strains of mice, the expression of Selenbp1 is suggested to be under the control of AhR. However, wasting syndrome by TCDD occurred equally in Selenbp1 (−/−) and (+/+) mice. The above pieces of evidence suggest that 1) Selenbp1 suppresses the expression of tumor-promoting genes although a reduction in Selenbp1 alone is not very serious as far as the animals are concerned; and 2) Selenbp1 induction by TCDD is neither a pre-requisite for toxicity nor a protective response for combating TCDD toxicity. Selenbp1 (−/−) mice exhibit little difference in their apparent phenotype and responsiveness to dioxin compared with the wild-type. This may be due to the compensation of Selenbp1 function by a closely-related protein, Selenbp2. •We generated Se-binding protein 1-null mice for clarifying its physiological role.•The null mice obtained exhibited little change in their apparent phenotypes.•However, the expression of many cancer-related genes in the ovary was changed.•Wasting syndrome caused by dioxin occurred equally both in KO and wild-type mice.